The dynamic nature of the K-Ras/calmodulin complex can be altered by oncogenic mutations

Hazem Abdelkarim, Nicholas Leschinsky, Hyunbum Jang, Avik Banerjee, Ruth Nussinov, Vadim Gaponenko*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Oncogenic mutant K-Ras promotes cancer cell proliferation, migration, invasion, and survival by assembling signaling complexes. To date, the functional and structural roles of K-Ras mutations within these complexes are incompletely understood despite their mechanistic and therapeutic significance. Here, we review recent advances in understanding specific binding between K-Ras and the calcium sensor calmodulin. This interaction positively and negatively regulates diverse functions of K-Ras in cancer, suggesting flexibility in K-Ras/calmodulin complex formation. Also, structural data suggest that oncogenic K-Ras likely samples several conformational states, influencing its distinct assemblies with calmodulin and with other proteins. Understanding how K-Ras interacts with calmodulin and with other partners is essential to discovering novel inhibitors of K-Ras in cancer.

Original languageEnglish
Pages (from-to)164-170
Number of pages7
JournalCurrent Opinion in Structural Biology
StatePublished - Dec 2021


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